Date of Award
Spring 5-15-2015
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Kinesiology and Health
First Advisor
Jeffrey S. Otis
Second Advisor
Christopher P. Ingalls
Third Advisor
Brett J. Wong
Fourth Advisor
Jeffrey C. Rupp
Abstract
Skeletal muscle injury results in functional deficits that can take several weeks to fully recover. Ultimate recovery of function is dependent on the muscle’s ability to regenerate, a highly coordinated process that involves transient muscle inflammation and the replacement of damaged myofibers. Instrumental in the inflammatory response, is the pro-inflammatory cytokine TNF-α. Expression of TNF-α is thought to be regulated, in part, by the stress sensing 70 kDa heat shock protein (Hsp70). However, it remains unclear how Hsp70 alters TNF-α following injury, and if so, how these changes affect skeletal muscle repair. Therefore, we up-regulated Hsp70 expression using 17-allylamino-17-demethoxygeldanamycin (17-AAG) prior to and following BaCl2-induced injury, and assessed TNF-α and myogenin content. Regenerating fiber cross-sectional area (CSA) and in vivo isometric torque were also analyzed in the weeks following the injury. Treatment of 17-AAG resulted in a ~5 fold increase in Hsp70 of the uninjured muscle, but did not affect any other biochemical, morphological or functional variables compared to controls. In the days following the injury, TNF-α and myogenin were elevated and directly correlated. At these earlier time points (≤7 days), treatment of 17-AAG increased TNF-α above that of the injured controls and resulted in a sustained increase in myogenin. However, no differences were observed in regenerating fiber CSA or in vivo torque production between the groups. Together, these data suggest that Hsp70 induction increases TNF-α and myogenin content following BaCl2-induced injury, but does not appear to alter skeletal muscle regeneration or attenuate functional deficits in otherwise healthy young mice.
DOI
https://doi.org/10.57709/7078981
Recommended Citation
Baumann, Cory W., "Heat Shock Protein 70 Regulates Tumor Necrosis Factor-Alpha and Myogenin in Skeletal Muscle Following Chemical-Induced Injury." Dissertation, Georgia State University, 2015.
doi: https://doi.org/10.57709/7078981